The partial control of dental caries by a well-controlled program of fluoridation of communal water and the health safety of the program has been established. Under support of Grant DEO-1850 we have applied ourselves to answering scientific questions and problems relating to biological processes other than caries that involve fluoride intake. There is need to continue investigations on the general health safety of excessive and deficient amounts of fluoride, and the possibility that beneficial effects other than dental caries reduction may result from optimal intakes. The fluoride intake from all sources (food, liquids, dentrifices, etc.) of individuals of various ages, living in the same and in different dietary regions of the United States will be further investigated. The role of fluoride in bone (resorption, formation and metabolism), lipid metabolism in general, caries prevention and its relation to other trace elements (Zn, Fe, etc.) in metabolism will be elucidated. The primary aim of this proposal is to continue to examine factors which are concerned with the biochemistry, physiology, and nutrition of fluoride. Its concentration, forms, and functions in body fluids, soft tissues, and calcified tissues will also be investigated. Calcified tissue metabolism as well as general metabolic effects will be investigated after long time exposure to high and low fluoride exposure and when specific findings occur that are related to other studies. The general theme of the program will be to investigate fluoride regulation and calcified tissue metabolism. Some of the specific points to be investigated are: (1) Daily fluoride intake of infants and toddlers, (2) interrelation between skeletal fluoride load and plasma fluoride levels, (3) determination of nonionic fluorine in human and non-human serum.